Apoptosis is such a schemed death of cells, of which a particular feature is an immediate death of cells. In 1970's, apoptosis was reported as a new conception for the death of cells [see "Int. Rev. Cytol.", 68, 251(1980)]. As compared with a necrosis which was an old conception for the death of cells already known in the art, apoptosis is characterized in that the period of time lapsed between the time of impartment of a stimulus of causing the death of cells by apoptosis and the time of occurrence of the death of cells by apoptosis is shorter than that for the necrosis, and also that apoptosis does involve no inflammation in the peripheral tissues of the cancer region, and so on. Afterwards, there have been reported that many anti-cancer drugs such as adriamycin and cisplatin have the activities of inducing the apoptosis on some of incubated cancer cells ["Cancer Res.", 53, 1845 (1993) and "Exp. Cell Res.", 211, 231 (1994)].
However, it has become clear now that adriamycin or cisplatin as the anti-cancer drug can have an activity of inducing the apoptosis of cells on the leukemia cells and on the experimental cancer cells which were artificially generated by carcinogen virus and the like, but that adriamycin or cisplatin does not induce apoptosis on many of the spontaneously generated human solid cancer cells [see "Rinsho Igaku", 21, No.9, 42-45 (1995)]. That is to say, there exist such human solid cancer cells which possess such property of not inducing the apoptosis by the anti-cancer drugs known and utilized in the art, and which are of the apoptosis-resistant type.
An human pancreatic adenocarcinoma cell, AsPC-1 cell, is a cancer cell described in "In Vitro", 18, 24 (1982)", and AsPC-1 cell exhibits a very strong apoptosis-resistance against such anti-cancer drugs as adriamycin, etc. While, another human pancreatic adenocarcinoma cell, BxPC-3 cell [described in "Cancer Investigation", 4, 15 (1986)], is susceptible to apoptosis. For example, it is already known that adriamycin can induce apoptosis on BxPC-3 cell within 24 hours from the start of treatment with adriamycin at the concentration of 3 .mu.g/ml, but adriamycin does not induce apoptosis on AsPC-1 cell even at the concentration of 30 .mu.g /ml of adriamycin.
In the past, nothing was known about such investigations which seek for the drugs capable of inducing the apoptosis on the apoptosis-resistant cancer cells such as the human pancreatic adenocarcinoma cell, AsPC-1 cell. In the clinical applications of conventional anti-cancer drugs of the type which can exhibit a cytotoxicity against cancer cells, it is considered that the "in vivo" contact time between the conventional anti-cancer drug and the cancer cells is a limited one. Thus, it is deducible that a more effective agent would be such an anti-cancer drug which is capable of inducing the apoptosis of cancer cells and thereby capable of making the cell death to be caused on the cancer cells in a shorter time than the conventional anti-cancer drug. It is further demanded to explore such a novel anti-cancer drug which is capable of inducing apoptosis and which is effective to cause apoptosis to effect even on such type of cancer cells insusceptible to induction of immediate death of cells by apoptosis, as long as they are treated by the known anti-cancer drug. It is therefore demanded now to provide such novel compounds which have an activity of inducing apoptosis effectively even on cancer cells of such type insusceptible to induction of apoptosis (immediate death of cells) when treated with the known anti-cancer drugs.